Chemotherapy and Radiation Therapy With or Without Metformin Hydrochloride in Treating Patients With Stage III Non-small Cell Lung Cancer

Randomized Phase II Trial of Concurrent Chemoradiotherapy +/- Metformin HCL in Locally Advanced NSCLC

This randomized phase II trial studies how well chemotherapy and radiation therapy given with or without metformin hydrochloride works in treating patients with stage III non-small cell lung cancer. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Metformin hydrochloride may shrink tumors and keep them from coming back. It is not yet known whether chemotherapy and radiation therapy is more effective when given with or without metformin hydrochloride in treating stage III non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Non-Small Cell Lung Cancer; Lung Adenocarcinoma; Recurrent Non-Small Cell Lung Carcinoma; Adenosquamous Lung Carcinoma; Bronchioloalveolar Carcinoma; Large Cell Lung Carcinoma; Squamous Cell Lung Carcinoma; Non-Small Cell Lung Carcinoma
• Intervention / Treatment: Radiation: Radiation Therapy; Drug: Carboplatin; Drug: Paclitaxel; Drug: Metformin

Detailed Description

PRIMARY OBJECTIVES:

I. To determine whether metformin hydrochloride (MET) added to chemoradiotherapy can improve progression-free survival (PFS) in patients with locally advanced non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:

I. Determine the effects of MET on overall survival (OS), time to local-regional progression (LRP), and time to distant metastasis (DM).

II. Evaluate the effect of MET on chemoradiotherapy toxicity (Common Terminology Criteria for Adverse Events, version 4 [CTCAE, v. 4]) within 1 year of completion of all treatment.

III. Collect biospecimens to develop biomarkers of MET activity.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

After completion of study treatment, patients are followed up at 4-6 weeks, every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• Israel
  • Tel Litwinsky, Israel, 52621
    • Chaim Sheba Medical Center
• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35401
      • Lewis and Faye Manderson Cancer Center
  • Arizona
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center - Tucson
  • California
    • Auburn, California, United States, 95603
      • Sutter Cancer Centers Radiation Oncology Services-Auburn
    • Cameron Park, California, United States, 95682
      • Sutter Cancer Centers Radiation Oncology Services-Cameron Park
    • Castro Valley, California, United States, 94546
      • Eden Hospital Medical Center
    • La Jolla, California, United States, 92093
      • UC San Diego Moores Cancer Center
    • Modesto, California, United States, 95355
      • Memorial Medical Center
    • Oakland, California, United States, 94611
      • Kaiser Permanente Oakland-Broadway
    • Rancho Cordova, California, United States, 95670
      • Kaiser Permanente-Rancho Cordova Cancer Center
    • Rohnert Park, California, United States, 94928
      • Rohnert Park Cancer Center
    • Roseville, California, United States, 95678
      • The Permanente Medical Group-Roseville Radiation Oncology
    • Roseville, California, United States, 95661
      • Sutter Cancer Centers Radiation Oncology Services-Roseville
    • Sacramento, California, United States, 95816
      • Sutter Medical Center Sacramento
    • Sacramento, California, United States, 95823
      • South Sacramento Cancer Center
    • San Francisco, California, United States, 94115
      • UCSF Medical Center-Mount Zion
    • South San Francisco, California, United States, 94080
      • Kaiser Permanente Cancer Treatment Center
    • Vacaville, California, United States, 95687
      • Sutter Cancer Centers Radiation Oncology Services-Vacaville
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital
    • Colorado Springs, Colorado, United States, 80907
      • Penrose-Saint Francis Healthcare
    • Colorado Springs, Colorado, United States, 80909
      • UCHealth Memorial Hospital Central
    • Englewood, Colorado, United States, 80113
      • Swedish Medical Center
    • Greeley, Colorado, United States, 80631
      • North Colorado Medical Center
    • Loveland, Colorado, United States, 80539
      • McKee Medical Center
    • Wheat Ridge, Colorado, United States, 80033
      • SCL Health Lutheran Medical Center
  • Delaware
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • Florida
    • Orlando, Florida, United States, 32806
      • UF Cancer Center at Orlando Health
    • Palatka, Florida, United States, 32177
      • 21st Century Oncology-Palatka
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Columbus, Georgia, United States, 31904
      • John B Amos Cancer Center
    • Decatur, Georgia, United States, 30033
      • Dekalb Medical Center
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Savannah, Georgia, United States, 31404
      • Memorial Health University Medical Center
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96817
      • The Cancer Center of Hawaii-Liliha
    • ‘Aiea, Hawaii, United States, 96701
      • The Cancer Center of Hawaii-Pali Momi
  • Idaho
    • Boise, Idaho, United States, 83706
      • Saint Alphonsus Cancer Care Center-Boise
    • Post Falls, Idaho, United States, 83854
      • Kootenai Cancer Center
    • Twin Falls, Idaho, United States, 83301
      • Saint Luke's Mountain States Tumor Institute-Twin Falls
  • Illinois
    • Arlington Heights, Illinois, United States, 60005
      • Northwest Community Hospital
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60612
      • John H Stroger Jr Hospital of Cook County
    • Decatur, Illinois, United States, 62526
      • Decatur Memorial Hospital
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
    • Pekin, Illinois, United States, 61554
      • OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • OSF Saint Francis Radiation Oncology at Peoria Cancer Center
    • Springfield, Illinois, United States, 62781
      • Memorial Medical Center
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Indiana
    • Bloomington, Indiana, United States, 47403
      • IU Health Bloomington
    • Fort Wayne, Indiana, United States, 46805
      • Parkview Hospital Randallia
    • Fort Wayne, Indiana, United States, 46804
      • Radiation Oncology Associates PC
    • Indianapolis, Indiana, United States, 46237
      • Franciscan Health Indianapolis
  • Iowa
    • Cedar Rapids, Iowa, United States, 52403
      • Mercy Hospital
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Cancer Center
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Overland Park, Kansas, United States, 66210
      • University of Kansas Cancer Center-Overland Park
    • Wichita, Kansas, United States, 67214
      • Ascension Via Christi Hospitals Wichita
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
  • Kentucky
    • Elizabethtown, Kentucky, United States, 42701
      • Hardin Memorial Hospital
    • Lexington, Kentucky, United States, 40536
      • University of Kentucky/Markey Cancer Center
    • Lexington, Kentucky, United States, 40503
      • Baptist Health Lexington
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70805
      • LSU Health Baton Rouge-North Clinic
    • Baton Rouge, Louisiana, United States, 70809
      • Louisiana Hematology Oncology Associates LLC
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center
    • Baton Rouge, Louisiana, United States, 70809
      • Our Lady of the Lake Physicians Group - Medical Oncology
    • Covington, Louisiana, United States, 70433
      • Mary Bird Perkins Cancer Center - Covington
    • Houma, Louisiana, United States, 70360
      • Mary Bird Perkins Cancer Center - Houma
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Medical Center- Scarborough Campus
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland/Greenebaum Cancer Center
    • Bel Air, Maryland, United States, 21014
      • UM Upper Chesapeake Medical Center
    • Glen Burnie, Maryland, United States, 21061
      • UM Baltimore Washington Medical Center/Tate Cancer Center
    • Salisbury, Maryland, United States, 21801
      • Peninsula Regional Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center
    • Lowell, Massachusetts, United States, 01854
      • Lowell General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Flint, Michigan, United States, 48532
      • McLaren Cancer Institute-Flint
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health at Butterworth Campus
    • Grand Rapids, Michigan, United States, 49503
      • Mercy Health Saint Mary's
    • Kalamazoo, Michigan, United States, 49007
      • West Michigan Cancer Center
    • Lapeer, Michigan, United States, 48446
      • McLaren Cancer Institute-Lapeer Region
    • Mount Clemens, Michigan, United States, 48043
      • McLaren Cancer Institute-Macomb
    • Mount Pleasant, Michigan, United States, 48858
      • McLaren Cancer Institute-Central Michigan
    • Muskegon, Michigan, United States, 49444
      • Mercy Health Mercy Campus
    • Owosso, Michigan, United States, 48867
      • McLaren Cancer Institute-Owosso
    • Petoskey, Michigan, United States, 49770
      • McLaren Cancer Institute-Northern Michigan
    • Pontiac, Michigan, United States, 48341
      • Saint Joseph Mercy Oakland
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hospital-Royal Oak
    • Saint Joseph, Michigan, United States, 49085
      • Lakeland Medical Center Saint Joseph
    • Troy, Michigan, United States, 48085
      • William Beaumont Hospital - Troy
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • Sanford Joe Lueken Cancer Center
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Duluth, Minnesota, United States, 55805
      • Saint Luke's Hospital of Duluth
    • Edina, Minnesota, United States, 55435
      • Fairview-Southdale Hospital
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
  • Missouri
    • Cape Girardeau, Missouri, United States, 63703
      • Saint Francis Medical Center
    • Cape Girardeau, Missouri, United States, 63703
      • Southeast Cancer Center
    • Kansas City, Missouri, United States, 64116
      • North Kansas City Hospital
    • Kansas City, Missouri, United States, 64131
      • The University of Kansas Cancer Center-South
    • Kansas City, Missouri, United States, 64154
      • The University of Kansas Cancer Center-North
    • Lee's Summit, Missouri, United States, 64064
      • The University of Kansas Cancer Center-Lee's Summit
    • Rolla, Missouri, United States, 65401
      • Delbert Day Cancer Institute at PCRMC
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • St Louis, Missouri, United States, 63131
      • Missouri Baptist Medical Center
    • St Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic Cancer Center
    • Missoula, Montana, United States, 59804
      • Community Medical Hospital
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • CHI Health Saint Francis
    • Kearney, Nebraska, United States, 68847
      • CHI Health Good Samaritan
    • Omaha, Nebraska, United States, 68114
      • Nebraska Methodist Hospital
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New Hampshire
    • Dover, New Hampshire, United States, 03820
      • Wentworth-Douglass Hospital
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Mount Holly, New Jersey, United States, 08060
      • Virtua Memorial
    • Toms River, New Jersey, United States, 08755
      • Community Medical Center
    • Voorhees Township, New Jersey, United States, 08043
      • Virtua Voorhees
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • University of New Mexico Cancer Center
    • Albuquerque, New Mexico, United States, 87109
      • New Mexico Oncology Hematology Consultants
  • New York
    • Brooklyn, New York, United States, 11215
      • New York-Presbyterian/Brooklyn Methodist Hospital
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Belmont, North Carolina, United States, 28012
      • Gaston Hematology and Oncology Associates-Belmont
    • Gastonia, North Carolina, United States, 28054
      • CaroMont Regional Medical Center
    • Gastonia, North Carolina, United States, 28054
      • Gaston Hematology and Oncology Associates
    • Pinehurst, North Carolina, United States, 28374
      • FirstHealth of the Carolinas-Moore Regional Hospital
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Sanford Bismarck Medical Center
    • Fargo, North Dakota, United States, 58122
      • Sanford Roger Maris Cancer Center
  • Ohio
    • Beachwood, Ohio, United States, 44122
      • UHHS-Chagrin Highlands Medical Center
    • Canton, Ohio, United States, 44710
      • Aultman Health Foundation
    • Canton, Ohio, United States, 44708
      • Mercy Medical Center
    • Chardon, Ohio, United States, 44024
      • Geauga Hospital
    • Chillicothe, Ohio, United States, 45601
      • Adena Regional Medical Center
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati/Barrett Cancer Center
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43214
      • Riverside Methodist Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center
    • Columbus, Ohio, United States, 43219
      • The Mark H Zangmeister Center
    • Columbus, Ohio, United States, 43222
      • Mount Carmel Health Center West
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Elyria, Ohio, United States, 44035
      • Mercy Cancer Center-Elyria
    • Independence, Ohio, United States, 44131
      • Cleveland Clinic Cancer Center Independence
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Mayfield Heights, Ohio, United States, 44124
      • Hillcrest Hospital Cancer Center
    • Mentor, Ohio, United States, 44060
      • UH Seidman Cancer Center at Lake Health Mentor Campus
    • Middleburg Heights, Ohio, United States, 44130
      • UH Seidman Cancer Center at Southwest General Hospital
    • Newark, Ohio, United States, 43055
      • Newark Radiation Oncology
    • Parma, Ohio, United States, 44129
      • University Hospitals Parma Medical Center
    • Portsmouth, Ohio, United States, 45662
      • Southern Ohio Medical Center
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care
    • Sandusky, Ohio, United States, 44870
      • UH Seidman Cancer Center at Firelands Regional Medical Center
    • Strongsville, Ohio, United States, 44136
      • Cleveland Clinic Cancer Center Strongsville
    • West Chester, Ohio, United States, 45069
      • University Pointe
    • Westlake, Ohio, United States, 44145
      • UHHS-Westlake Medical Center
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic Wooster Family Health and Surgery Center
    • Zanesville, Ohio, United States, 43701
      • Genesis Healthcare System Cancer Care Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Danville, Pennsylvania, United States, 17822
      • Geisinger Medical Center
    • Dunmore, Pennsylvania, United States, 18512
      • Northeast Radiation Oncology Center
    • Erie, Pennsylvania, United States, 16505
      • The Regional Cancer Center
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC-Shadyside Hospital
    • West Reading, Pennsylvania, United States, 19611
      • Reading Hospital
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Geisinger Wyoming Valley/Henry Cancer Center
    • Wynnewood, Pennsylvania, United States, 19096
      • Lankenau Medical Center
  • South Carolina
    • Anderson, South Carolina, United States, 29621
      • AnMed Health Cancer Center
    • Greenville, South Carolina, United States, 29607
      • Saint Francis Cancer Center
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System Cancer Institute-Faris
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System Cancer Institute-Eastside
    • Greenwood, South Carolina, United States, 29646
      • Self Regional Healthcare
    • Greer, South Carolina, United States, 29651
      • Gibbs Cancer Center-Pelham
    • Greer, South Carolina, United States, 29650
      • Greenville Health System Cancer Institute-Greer
    • Seneca, South Carolina, United States, 29672
      • Greenville Health System Cancer Institute-Seneca
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Center
    • Spartanburg, South Carolina, United States, 29307
      • Greenville Health System Cancer Institute-Spartanburg
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5134
      • Sanford USD Medical Center - Sioux Falls
  • Texas
    • Galveston, Texas, United States, 77555-0565
      • University of Texas Medical Branch
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
    • Houston, Texas, United States, 77094
      • MD Anderson in Katy
    • Houston, Texas, United States, 77030
      • The Methodist Hospital System
    • League City, Texas, United States, 77573
      • UTMB Cancer Center at Victory Lakes
    • Nassau Bay, Texas, United States, 77058
      • MD Anderson League City
    • Sugar Land, Texas, United States, 77478
      • MD Anderson in Sugar Land
    • The Woodlands, Texas, United States, 77384
      • MD Anderson in The Woodlands
  • Utah
    • Murray, Utah, United States, 84107
      • Intermountain Medical Center
  • Vermont
    • Berlin Corners, Vermont, United States, 05602
      • Central Vermont Medical Center/National Life Cancer Treatment
    • Burlington, Vermont, United States, 05401
      • University of Vermont Medical Center
    • Saint Johnsbury, Vermont, United States, 05819
      • Norris Cotton Cancer Center-North
  • Virginia
    • Fishersville, Virginia, United States, 22939
      • Augusta Health Center for Cancer and Blood Disorders
  • Washington
    • Bremerton, Washington, United States, 98310
      • Harrison Medical Center
    • Longview, Washington, United States, 98632
      • PeaceHealth Saint John Medical Center
    • Vancouver, Washington, United States, 98664
      • PeaceHealth Southwest Medical Center
  • West Virginia
    • Wheeling, West Virginia, United States, 26003
      • Wheeling Hospital/Schiffler Cancer Center
  • Wisconsin
    • Grafton, Wisconsin, United States, 53024
      • Aurora Cancer Care-Grafton
    • Green Bay, Wisconsin, United States, 54311
      • Aurora BayCare Medical Center
    • Kenosha, Wisconsin, United States, 53142
      • Aurora Cancer Care-Kenosha South
    • Marinette, Wisconsin, United States, 54143
      • Bay Area Medical Center
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Medical Center-Marshfield
    • Menomonee Falls, Wisconsin, United States, 53051
      • Community Memorial Hospital
    • Mequon, Wisconsin, United States, 53097
      • Ascension Columbia Saint Mary's Hospital Ozaukee
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Saint Luke's Medical Center
    • Milwaukee, Wisconsin, United States, 53295
      • Zablocki Veterans Administration Medical Center
    • Milwaukee, Wisconsin, United States, 53211
      • Ascension Columbia Saint Mary's Water Tower Medical Commons
    • Minocqua, Wisconsin, United States, 54548
      • Marshfield Clinic-Minocqua Center
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin
    • Rice Lake, Wisconsin, United States, 54868
      • Marshfield Medical Center-Rice Lake
    • Stevens Point, Wisconsin, United States, 54481
      • Saint Michael's Hospital
    • Summit, Wisconsin, United States, 53066
      • Aurora Medical Center in Summit
    • Two Rivers, Wisconsin, United States, 54241
      • Vince Lombardi Cancer Clinic-Two Rivers
    • West Allis, Wisconsin, United States, 53227
      • Aurora West Allis Medical Center
    • West Bend, Wisconsin, United States, 53095
      • The Alyce and Elmore Kraemer Cancer Care Center
    • Weston, Wisconsin, United States, 54476
      • Diagnostic and Treatment Center
    • Wisconsin Rapids, Wisconsin, United States, 54494
      • Aspirus UW Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of stage IIIA or IIIB non-small cell lung cancer within 84 days of registration; eligible histologies include adenocarcinoma, adenosquamous, large cell carcinoma, squamous carcinoma, non-lobar and non-diffuse bronchoalveolar cell carcinoma or non-small cell lung cancer not otherwise specified)
• Patients must have measurable disease
• Patients must have unresectable disease, be medically inoperable, or unwilling to undergo surgical management

• Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup:

  • History/physical examination, including documentation of height, weight, body surface area, and vital signs, within 30 days prior to registration
  • Computed tomography (CT) with IV contrast or magnetic resonance imaging (MRI) imaging (if CT scan with contrast is medically contraindicated) of the lung and upper abdomen through the adrenal glands, required within 45 days prior to registration (recommended within 30 days prior to registration
  • MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated) within 45 days prior to registration; note: the use of intravenous contrast is required for the MRI or CT; an MRI without contrast is only permitted if the patient has a contrast allergy
  • Whole-body fludeoxyglucose (FDG)-positron emission tomography (PET)/CT required within 45 days prior to registration (recommended within 30 days prior to registration; note: patients do not need to have a separate CT of the chest and upper abdomen with contrast if PET/CT imaging includes a high quality CT with contrast
• Zubrod performance status 0-1
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3

• Complete blood count(CBC)/differential obtained within 14 days prior to registration on study, with adequate bone marrow function defined as follows:

  • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
  • Platelets >= 100,000 cells/mm^3
  • Hemoglobin >= 8.0 g/dl (note: the use of transfusion or other intervention to achieve hemoglobin [Hgb] >= 8.0 g/dl is acceptable)
• Adequate renal function within 14 days prior to registration, defined as serum creatinine within normal institutional limits or creatinine clearance must be at least 60 ml/min;
• Adequate hepatic function within 14 days prior to registration, defined as total bilirubin ≤ 1.5 x upper limit of normal (ULN) for the institution and alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase ≤ 2.5 x ULN for the institution;
• Fasting blood glucose ≤ 125 mg/dL within 14 days prior to registration;
• Serum albumin > 3.0 g/dl within 14 days prior to registration;
• For women of childbearing potential, a serum pregnancy test within 72 hours prior to registration;
• Patients with post-obstructive pneumonia are eligible provided they no longer require intravenous antibiotics at registration;
• Patients must be at least 3 weeks from prior thoracotomy (if performed);

• If a pleural effusion is present, the following criteria must be met at registration to exclude malignant involvement (incurable M1a disease):

  • When pleural fluid is visible on both the CT scan and on a chest x-ray, a pleuracentesis is required to confirm that the pleural fluid is cytologically negative;
  • Effusions that are minimal (i.e. not visible under ultrasound guidance) and that are too small to safely tap are eligible.
• Women of childbearing potential and male participants must practice adequate contraception throughout the study;

Exclusion Criteria:

• Patients with mixed small cell and non-small cell histologies
• Patients with distant metastasis
• Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible)
• Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable
• Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• Patients currently using metformin (metformin hydrochloride), other oral hypoglycemic agents or insulin
• Patients with any history of allergic reaction to paclitaxel or other taxanes or carboplatin
• Patients with a history of chronic kidney disease or lactic acidosis
• Patients with >= 10% weight loss within the past month

• Severe, active co-morbidity, defined as follows:

  • Diagnosis of type I or type II diabetes mellitus
  • Uncontrolled neuropathy >= grade 2 regardless of cause
  • Unstable angina and/or congestive heart failure requiring hospitalization within the last 6 months
  • Transmural myocardial infarction within the last 6 months
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
  • Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days of registration
  • Severe hepatic disease, defined as a diagnosis of Child-Pugh class B or C hepatic disease
  • Human immunodeficiency virus (HIV) positive with cluster of differentiation (CD)4 count < 200 cells/microliter; note that patients who are HIV positive are eligible, provided they are under treatment with highly active antiretroviral therapy (HAART) and have a CD4 count >= 200 cells/microliter within 30 days prior to registration; note also that HIV testing is not required for eligibility for this protocol
  • End-stage renal disease (ie, on dialysis or dialysis has been recommended)
• Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Chemoradiation; 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin	Radiation: Radiation Therapy; Radiation therapy (RT) is given in 2 Gy fractions once daily 5 days per week to a total of 30 fractions and 60 Gy. Photons required; 3-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) permitted. Starts within 14 days of randomization (Chemoradiation arm) or 14 days after metformin starts (Chemoradiation + Metformin arm).; Other Names: 3-dimensional conformal radiation therapy; 3D-CRT; IMRT; Intensity-modulated radiation therapy; Drug: Carboplatin; 2 AUC (area under the curve) via IV weekly on days 1, 8, 15, 22, 29, and 36 from start of radiation therapy. Two 21 day cycles of 6 AUC via IV starting 28-42 days after the end of radiation therapy.; Drug: Paclitaxel; 50 mg/m2 via IV weekly on days 1, 8, 15, 22, 29, and 36 from start of radiation therapy. Two 21 day cycles of 200 mg/m2 via IV 28-42 days after the end of radiation therapy.
Experimental: Metformin + Chemoradiation; Metformin plus 60 Gy Radiation therapy with concurrent paclitaxel and carboplatin followed by consolidation paclitaxel and carboplatin	Radiation: Radiation Therapy; Radiation therapy (RT) is given in 2 Gy fractions once daily 5 days per week to a total of 30 fractions and 60 Gy. Photons required; 3-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) permitted. Starts within 14 days of randomization (Chemoradiation arm) or 14 days after metformin starts (Chemoradiation + Metformin arm).; Other Names: 3-dimensional conformal radiation therapy; 3D-CRT; IMRT; Intensity-modulated radiation therapy; Drug: Carboplatin; 2 AUC (area under the curve) via IV weekly on days 1, 8, 15, 22, 29, and 36 from start of radiation therapy. Two 21 day cycles of 6 AUC via IV starting 28-42 days after the end of radiation therapy.; Drug: Paclitaxel; 50 mg/m2 via IV weekly on days 1, 8, 15, 22, 29, and 36 from start of radiation therapy. Two 21 day cycles of 200 mg/m2 via IV 28-42 days after the end of radiation therapy.; Drug: Metformin; Metformin is taken orally. Dose escalation begins 2 weeks prior to the initiation of chemoradiation. 500 mg twice daily days 1-7 of metformin. 500 mg three times daily days 8-14 of metformin. Three times a day with the following dosage: 500mg in the morning, 1000mg at noon, and 500mg in the evening concurrent with chemoradiation and through consolidation chemotherapy (days 15-126 of metformin),; Other Names: Metformin Hydrochloride; Metformin HCL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Alive Without Progression (Progression-free Survival)	Progression is defined per RECIST v1.1 as change in a known lesion(s) meeting one of the following criteria: [1] At least a 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be > 5 mm. [2] Appearance of ≥1 new lesions. Progression-free survival time is defined as time from randomization to the date of first progression, death, or last known follow-up (censored). Progression-free survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Alive (Overall Survival)	Overall survival time is defined as time from randomization to the date of death from any cause or last known follow-up (censored). Overall survival rates are estimated using the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
Percentage of Participants With Local-regional Progression	Local-regional progression (LRP) is defined as progression within the planned treatment volume (PTV) or outside the PTV but within the same lobe(s) of the lung as the primary tumor or in regional lymph nodes. Progression is defined as change in a known lesion(s) meeting one of the following criteria: [1] ≥ 20% increase in the sum of the longest diameter of target lesions such that the absolute increase must be > 5 mm. [2] Appearance of ≥1 new lesions. LRP time is defined as time from randomization to the date of first LRP, death without LRP (competing risk), or last known follow-up (censored). LRP rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 LRP events were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
Percentage of Participants With Distant Metastases	Distant metastasis (DM) is defined as the appearance of ≥ 1 new lesions at any site (including pleural or pericardial effusion) outside of the following: the planned treatment volume, the same lobe(s) of the lung as the primary tumor, or regional lymph nodes. Time to DM is defined as time from randomization to the date of first DM, death without DM (competing risk), or last known follow-up (censored). DM rates are estimated using the cumulative incidence method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after 102 progression-free survival events were reported.	From randomization to last follow-up. Maximum follow-up at time of analysis was 47.2 months.
Percentage of Participants With Treatment-related Grade 3 or Higher Adverse Events	Adverse events (AE) were graded using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Grade refers to the severity of the AE. The CTCAE v4.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to adverse event. "Treatment-related" is defined definitely, probably, or possibly related to treatment.	From start of treatment to last follow-up. Maximum follow-up at time of analysis was 47.2 months.

Collaborators and Investigators

• Sponsor: NRG Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Theodoros Tsakiridis, NRG Oncology

Publications and helpful links

General Publications

• Skinner H, Hu C, Tsakiridis T, Santana-Davila R, Lu B, Erasmus JJ, Doemer AJ, Videtic GMM, Coster J, Yang AX, Lee RY, Werner-Wasik M, Schaner PE, McCormack SE, Esparaz BT, McGarry RC, Bazan J, Struve T, Paulus R, Bradley JD. Addition of Metformin to Concurrent Chemoradiation in Patients With Locally Advanced Non-Small Cell Lung Cancer: The NRG-LU001 Phase 2 Randomized Clinical Trial. JAMA Oncol. 2021 Sep 1;7(9):1324-1332. doi: 10.1001/jamaoncol.2021.2318.

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Actual): April 16, 2019
• Study Completion (Actual): September 4, 2025

Study Registration Dates

• First Submitted: July 8, 2014
• First Submitted That Met QC Criteria: July 8, 2014
• First Posted (Estimated): July 10, 2014

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Neoplasms by Histologic Type; Lung Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Bronchial Neoplasms; Adenocarcinoma of Lung; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma, Bronchiolo-Alveolar; Organic Chemicals; Therapeutics; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Biguanides; Guanidines; Amidines; Radiotherapy, Computer-Assisted; Metformin; Carboplatin; Paclitaxel; Radiotherapy; Radiotherapy, Intensity-Modulated; Radiotherapy, Conformal
• Other Study ID Numbers: NRG-LU001 (Other Identifier: CTEP); U10CA180868 (U.S. NIH Grant/Contract); NCI-2014-01071 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); PNRG-LU001_A01PAMDREVW01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.